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1.
BMC Surg ; 24(1): 134, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702689

ABSTRACT

OBJECTIVES: A considerable number of patients are diagnosed with prostate cancer (PCa) by transurethral resection of the prostate (TURP). We aimed to evaluate whether radical prostatectomy (RP) brings survival benefits for these patients, especially in the elderly with advanced PCa. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to obtain PCa cases diagnosed with TURP. After the propensity matching score (PSM) for case matching, univariate, multivariate, and subgroup analyses were performed to investigate whether RP impacts the survival benefit. RESULTS: 4,677 cases diagnosed with PCa by TURP from 2010 to 2019 were obtained, including 1,313 RP patients and 3,364 patients with no RP (nRP). 9.6% of RP patients had advanced PCa. With or without PSM, cancer-specific mortality (CSM) and overall mortality (OM) were significantly reduced in the RP patients compared to the nRP patients, even for older (> 75 ys.) patients with advanced stages (all p < 0.05). Except for RP, younger age (≤ 75 ys.), being married, and earlier stage (localized) contributed to a significant reduction of CSM risk (all p < 0.05). These survival benefits had no significant differences among patients of different ages, married or single, and at different stages (all p for interaction > 0.05). CONCLUSIONS: Based on this retrospective population-matched study, we first found that in patients diagnosed with PCa by TURP, RP treatment may lead to a survival benefit, especially a reduction in CSM, even in old aged patients (> 75 ys.) with advanced PCa.


Subject(s)
Prostatectomy , Prostatic Neoplasms , SEER Program , Transurethral Resection of Prostate , Humans , Male , Prostatic Neoplasms/surgery , Prostatic Neoplasms/mortality , Prostatic Neoplasms/diagnosis , Aged , Prostatectomy/methods , Middle Aged , Propensity Score , Retrospective Studies , Neoplasm Staging , Survival Rate/trends
2.
Front Oncol ; 14: 1366766, 2024.
Article in English | MEDLINE | ID: mdl-38706599

ABSTRACT

ALK-positive Histiocytosis (ALK-HSs) is a recently identified rare clinical entity characterized by tissue histiocytic alterations associated with ALK gene rearrangement. Clinical presentations can be solitary, multifocal, or systemic (involving multiple sites and organs). Due to limited reported cases, there is inadequate understanding of this disease. This report presents a case of ALK-HSs in a 71-year-old male patient who presented with hematuria for one week. Imaging studies conducted at an external hospital showed multiple lesions in the penis, bilateral testes, back skin, and the third lumbar vertebra. Histopathological findings included spindle and histiocytic cell proliferation with mild or indistinct cellular atypia, interstitial infiltration of lymphocytes, plasma cells, foamy histiocytes, and fibrous tissue proliferation. Immunohistochemistry of the lesion cells revealed positivity for CD68, CD163, ALK1, ALK (D5F3), and Vimentin. FISH testing indicated ALK gene separation in the lesion cells. NGS testing identified the fusion genes KIF5B(NM_004521) and ALK(NM_004304) in the lesion cells. We combined the characteristics of this case with a review of the literature to enhance our understanding of this rare clinical entity.

3.
Diab Vasc Dis Res ; 21(2): 14791641241244658, 2024.
Article in English | MEDLINE | ID: mdl-38597578

ABSTRACT

BACKGROUND: The intricate interaction between oxidative stress and atherosclerotic cardiovascular disease (ASCVD) is an essential area of research because of the potential role of oxidative homeostasis in regulating ASCVD risk. This study aimed to investigate the relationship between the oxidative balance score (OBS) and the 10-years risk of ASCVD to gain insight into how oxidative balance affects cardiovascular health. METHODS: This cross-sectional study analyzed National Health and Nutrition Examination Survey (NHANES) 2011-2020 data (40-79 age group), exploring OBS's link to 10-years ASCVD risk. OBS categorized dietary and lifestyle factors. Multivariate logistic regression controlled for age, sex, race, and demographics. A restricted cubic spline examined linear relationships; robustness was ensured through subgroup analyses. RESULTS: Analysis of 4955 participants reveals a negative association between OBS and 10-years ASCVD risk. Continuous OBS adjusted OR: 0.97 (95% CI: 0.95∼0.99, p < .001). Quartile analysis shows reduced risk in Q2 0.88 (95% CI: 0.63∼1.22, p = .43), Q3 0.92 (95% CI: 0.66∼1.28, p = .614), and Q4 0.59 (95% CI: 0.42∼0.83, p = .002) compare Q1. Quartile analysis indicated decreasing risk in higher OBS quartiles. Lifestyle OBS and Dietary OBS demonstrated similar trends. Stratified analyses highlight race and hypertension as effect modifiers (p < .05). CONCLUSION: Our study suggests an association between higher OBS and a reduced 10-years ASCVD risk. However, causation should not be inferred, and in the future, more extensive clinical and fundamental research is required to delve deeper into this association.


Subject(s)
Atherosclerosis , Cardiovascular Diseases , Humans , Nutrition Surveys , Cross-Sectional Studies , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Oxidative Stress
4.
Article in English | MEDLINE | ID: mdl-38619196

ABSTRACT

BRCA1-associated RING domain protein 1 (BARD1) gene polymorphisms may be associated with neuroblastoma (NB) susceptibility. However, the results remain controversial. Relevant studies were identified by searching PubMed, Web of Science, Embase, China National Knowledge Infrastructure databases up to March 5, 2023. The strength of the association between BARD1 polymorphisms and susceptibility of NB was assessed by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs) through the fixed- or random-effects model. Eight articles involving 12 studies were finally included. We found that rs6435862 T > G, rs3768716 A > G, rs17487792 C > T and rs7587476 C > T variant increase the risk of NB in allelic, dominant, recessive, homozygous and heterozygous genetic models, while rs7585356 G > A variant appeared protective against NB. When stratified by ethnicity, subgroup analysis indicated that the above association remained significant in Caucasian populations in all genetic models, except for rs7585356G > A polymorphism in Asians. In Asian populations, we found the similar results in the allelic and dominant model of rs6435862 T > G, rs3768716 A > G, rs17487792 C > T and rs7587476 C > T as in Caucasians, while there lacked a significant association in the other three model. In addition, rs7585356 G > A was not associated with an increased risk of NB in the Asian population. After Bonferroni correction, significant associations for rs7585356 G > A disappeared in both Asian and Caucasian populations, with no significant association found for rs7587476 in the allelic and dominant models among Asians. BARD1 polymorphisms might be significantly associated with NB susceptibility. It is crucial that these finding should be further confirmed through extensive and well-planned studies.

5.
Biochem Biophys Res Commun ; 682: 148-155, 2023 11 19.
Article in English | MEDLINE | ID: mdl-37806254

ABSTRACT

Silencing type information regulator homolog 1 (SIRT1) is a class of nicotinamide adenine dinucleotide (NAD+) dependent deacetylases, which is the convergence point of important physiological processes in vivo, namely, osteoblast aging, energy metabolism, and bone remodeling. To verify whether the O-acetylglucosamine (O-GlcNAc) modification of SIRT1 in the nucleus of osteoblasts enhances its deacetylase activity under stress and protects osteoblasts through the RANK/RANKL signaling pathway by collagen deacetylation. The R language and online data research identified SIRT1 as being involved in bone metabolism. Enrichment analysis showed that SIRT1 is involved in osteoblast transcription, apoptosis, and deacetylation pathways. Interactive Immuno-blotting and immunofluorescence experiments revealed that SIRT1 and O-glycosylation catalytic enzyme (OGT) were localized in the nucleus. Mass Spectrometry analysis showed that O-glycosylation occurred on the asparagine at the 346th position of SIRT1, and N346th was located in the central domain of SIRT1. Furthermore, the protein structure analysis of PyMol also proved that the OGT binding region was in the central domain of SIRT1. Under physiological conditions, both wtSIRT1 and SIRT1N346R can inhibit RANKL-mediated transcriptional activation. The RT-PCR detection results showed that wtSIRT1 reduced RANKL transcription under the conditions of apoptotic agent treatment. The finding that SIRT1 can regulate the physiological process of bone remodeling through the RANK/RANKL signaling pathway in osteoblasts under stress. The O-glycosylation and deacetylation activity of SIRT1 significantly increased, regulating the balance between osteoblast survival and apoptosis by deacetylation of key proteins such as RANKL.


Subject(s)
Sirtuin 1 , Sugars , Sirtuin 1/genetics , Sirtuin 1/metabolism , Sugars/metabolism , Collagen Type I/metabolism , NAD/metabolism , Osteoblasts/metabolism
6.
Front Pediatr ; 11: 1209359, 2023.
Article in English | MEDLINE | ID: mdl-37780043

ABSTRACT

Objective: To investigate the clinical effect of the da Vinci robotic-assisted laparoscopic pyeloureteroplasty (RALP) in treating pediatric ureteropelvic junction obstruction (UPJO). Methods: We retrospectively analyzed clinical data from 32 children with UPJO who suffered from RALP in our hospital from October 2020 to February 2023, compared with those treated with common laparoscopy at the same time. After the establishment of the robotic arm, a mesenteric approach was performed after entering the abdominal cavity to focus on the lesion site. The dilated renal pelvis was then cut and the stenotic ureter was removed; the anastomosis and the incision were sutured by layer. Results: A total of 62 children (44 boys and 20 girls) with a median age of 14 months (ranging from 3 to 38 months) were included. All 62 cases had hydronephrosis caused by unilateral UPJO, and the surgery was successfully completed without conversion to open. All intraoperative blood losses amounted to less than 10 ml. In the RALP group, the average operative duration was 131.28 min (ranging from 108 to 180 min). The average catheter time was 3.66 days (ranging from 2 to 7 days). The average hematuria time was 3.84 days (ranging from 2 to 6 days). The average postoperative hospital stay was 7.8 days (ranging from 6 to 12 days). The average hospitalization costs were 59,048.31 yuan (ranging from 50,484 to 69,977 yuan). The double-J tube was removed 1 month after surgery. Only one patient suffered from complications, developing a urinary tract infection 4 weeks after surgery, and was cured with the administration of oral cefaclor anti-inflammatory drugs for 3 days. All patients were followed up for 2-28 months, with a median follow-up time of 12 months. The thickness of the renal cortex was increased after surgery [(1.95 ± 0.24) vs. (4.82 ± 0.50)] cm, and the isotope renograms revealed a definite recovery of the split renal function [(28.32 ± 1.95) vs. (37.01 ± 2.71)]%. Conclusion: The robotic-assisted laparoscopic pyeloureteroplasty (RALP) in the treatment of children with upper ureteral obstruction has overall clinical efficiency. With technological advancements and an increased number of experienced surgeons, robotic surgery may become a new trend in surgery.

7.
Bioresour Technol ; 387: 129648, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37572887

ABSTRACT

This study used metagenomic sequencing to examine the effects of carbon-based zinc oxide nanoparticles (CZnONPs) and graphene-based zinc oxide nanoparticles (GZnONPs) on quorum sensing (QS), antibiotic resistance genes (ARGs) and microbial community changes during cattle manure production. The manure zinc content was significantly reduced in GZnONPs group. In the QS pathway, the autoinducer gene increases significantly in Control group, while the transporter and repressor genes experience a substantial increase in CZnONPs group. These results contributed to the significantly decreased the abundance of ARGs in GZnONPs group. The co-occurrence network analysis revealed a correlation between core ARGs and QS-related KEGG Orthology or ARGs' hosts, indicating that the selective pressure of zinc influences microbial QS, forming a unique ARG pattern in in vivo anaerobic fermentation. These findings suggest that implementing nutritional regulation in farming practices can serve as a preventive measure to mitigate the potential transmission of ARGs resulting from livestock waste.


Subject(s)
Microbiota , Nanostructures , Zinc Oxide , Cattle , Animals , Manure , Genes, Bacterial , Zinc , Carbon , Anti-Bacterial Agents/pharmacology , Quorum Sensing/genetics , Drug Resistance, Microbial/genetics
8.
Ecotoxicol Environ Saf ; 263: 115277, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37499390

ABSTRACT

Numerous antibiotic resistance genes (ARGs) and virulence factors (VFs) found in animal manure pose significant risks to human health. However, the effects of graphene sodium selenite (GSSe), a novel chemical nano-Selenium, and biological nano-Selenium (BNSSe), a new bioaugmentation nano-Se, on bacterial Se metabolism, chemotaxis, ARGs, and VFs in animal manure remain unknown. In this study, we investigated the effects of GSSe and BNSSe on ARGs and VFs expression in broiler manure using high-throughput sequencing. Results showed that BNSSe reduced Se pressure during anaerobic fermentation by inhibiting bacterial selenocompound metabolism pathways, thereby lowering manure Selenium pollution. Additionally, the expression levels of ARGs and VFs were lower in the BNSSe group compared to the Sodium Selenite and GSSe groups, as BNSSe inhibited bacterial chemotaxis pathways. Co-occurrence network analysis identified ARGs and VFs within the following phyla Bacteroidetes (genera Butyricimonas, Odoribacter, Paraprevotella, and Rikenella), Firmicutes (genera Lactobacillus, Candidatus_Borkfalkia, Merdimonas, Oscillibacter, Intestinimonas, and Megamonas), and Proteobacteria (genera Desulfovibrio). The expression and abundance of ARGs and VFs genes were found to be associated with ARGs-VFs coexistence. Moreover, BNSSe disruption of bacterial selenocompound metabolism and chemotaxis pathways resulted in less frequent transfer of ARGs and VFs. These findings indicate that BNSSe can reduce ARGs and VFs expression in animal manure by suppressing bacterial selenocompound metabolism and chemotaxis pathways.


Subject(s)
Selenium , Humans , Animals , Selenium/pharmacology , Manure/analysis , Genes, Bacterial , Anti-Bacterial Agents/pharmacology , Chemotaxis/genetics , Sodium Selenite/pharmacology , Chickens/genetics , Bacteria , Drug Resistance, Microbial/genetics , Bacteroidetes , Firmicutes
9.
Sci Total Environ ; 881: 163520, 2023 Jul 10.
Article in English | MEDLINE | ID: mdl-37061060

ABSTRACT

Animal manure contains many antibiotic resistance genes (ARGs) and virulence factors (VFs), posing significant health threats to humans. However, the effects of graphene nano zinc oxide (GZnONP), a zinc bioaugmentation substitute, on bacterial chemotaxis, ARGs, and VFs in animal manure remain scanty. Herein, the effect of GZnONP on the in vivo anaerobic expression of ARGs and VFs in cattle manure was assessed using high-throughput sequencing. Results showed that GZnONP inhibited bacterial chemotaxis by reducing the zinc pressure under anaerobic fermentation, altering the microbial community structure. The expression of ARGs was significantly lower in GZnONP than in zinc oxide and nano zinc oxide (ZnONP) groups. The expression of VFs was lower in the GZnONP than in the zinc oxide and ZnONP groups by 9.85 % and 13.46 %, respectively. Co-occurrence network analysis revealed that ARGs and VFs were expressed by the Spirochaetes phylum, Paraprevotella genus, and Treponema genus et al. The ARGs-VFs coexistence was related to the expression/abundance of ARGs and VFs genes. GZnONP reduces the abundance of certain bacterial species by disrupting chemotaxis, minimizing the transfer of ARGs and VFs. These findings suggest that GZnONP, a bacterial chemotaxis suppressor, effectively reduces the expression and release of ARGs and VFs in animal manure.


Subject(s)
Graphite , Zinc Oxide , Humans , Animals , Cattle , Anti-Bacterial Agents/pharmacology , Zinc/pharmacology , Manure/microbiology , Genes, Bacterial , Zinc Oxide/pharmacology , Drug Resistance, Microbial/genetics , Bacteria/genetics
10.
Phytomedicine ; 109: 154554, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36610159

ABSTRACT

BACKGROUND: The incidence of cardiovascular events remains not unusual in patients following percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Chinese patent medicine (CPM) therapy based on syndrome differentiation in addition to conventional medicine (CM) had been expected to further reduce the risk of cardiovascular events. PURPOSE: To assess the effectiveness and safety of CPM based on syndrome differentiation in patients following PCI due to ACS. STUDY DESIGN: Nationwide prospective cohort study. METHODS: CPM study was conducted in 40 centers in mainland China. Patients following PCI due to ACS entered to syndrome differentiation-based CPM (SDCPM) or CM group according to whether they received CPM or not. The CPM comprised Guanxin Danshen dripping pills, Qishen Yiqi dripping pills, or Danlou tablets, and was used correspondingly with the syndrome differentiation of traditional Chinese medicine. The follow-up time was 36 months. The primary endpoint was composed of cardiac death, non-fatal myocardial infarction and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, other thrombotic events. Seattle Angina Questionnaire (SAQ) was used to evaluate quality of life. RESULTS: Between February 2012 and December 2018, ascertainment of the primary endpoint was completed in 2,724 patients of follow-up. 1,380 patients were in SDCPM group. At a median follow-up of 541 (interquartile range 513 - 564) days, the primary endpoint occurred in 126 (8.61%) patients in SDCPM group and 167 (11.62%) patients in CM group (adjusted hazard ratio [HR] = 0.70; [95% confidence interval [CI] 0.55 - 0.89]; p = 0.003). The secondary endpoint occurred in 144 (9.84%) patients in SDCPM group and 197 (13.71%) patients in CM group (adjusted HR = 0.66; [95% CI 0.53 - 0.82]; p < 0.001). The SAQ score in SDCPM group was higher than CM group (366.78 ± 70.19 vs 356.43 ± 73.80, p < 0.001). There were no significant differences of adverse events between two groups. CONCLUSION: In patients following PCI due to ACS, SDCPM in addition to CM treatment reduced the primary and secondary endpoints, as well as improved the quality of life without adverse events.


Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Humans , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/etiology , Cohort Studies , Percutaneous Coronary Intervention/adverse effects , Prospective Studies , Quality of Life , Treatment Outcome
11.
Mol Neurobiol ; 60(5): 2729-2736, 2023 May.
Article in English | MEDLINE | ID: mdl-36717479

ABSTRACT

Increasing evidence suggests that circadian dysfunction is related to Parkinson's disease (PD). However, the role of circadian clock genes in PD is still poorly understood. This study aimed to illustrate the association between genetic variants of circadian clock genes and PD in a large Chinese population cohort. Ten circadian clock genes were included in this study. Whole-exome sequencing (WES) was conducted in 1997 early-onset or familial PD patients and 1652 controls (WES cohort), and whole-genome sequencing (WGS) was conducted in 1962 sporadic late-onset PD patients and 1279 controls (WGS cohort). Analyses were completed using the optimized sequence kernel association test and regression analyses. In the burden analysis of the circadian clock gene set, we found suggestive significant associations between the circadian clock genes and PD in the WES cohort when considering missense, damaging missense (Dmis), and deleterious variants. Moreover, the burden analysis of single genes revealed suggestive significant associations between PD and the loss-of-function variants of the CRY1 gene, missense, Dmis, and deleterious variants of the PER1 gene, and Dmis and deleterious variants of the PER2 gene in the WES cohort. Rare variants in the WGS cohort and all common variants in the WGS and WES cohorts were unrelated to PD. Phenotypic analysis indicated that deleterious variants of the PER1 gene were associated with dyskinesia in the WES cohort. Our study provides evidence of a potential link between circadian clock genes and PD from a genetic perspective.


Subject(s)
Circadian Clocks , Parkinson Disease , Humans , Parkinson Disease/genetics , Circadian Clocks/genetics , Exome Sequencing , Asian People
12.
BMC Vet Res ; 18(1): 425, 2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36474293

ABSTRACT

BACKGROUND: To our knowledge, carbon loaded with nano-ZnO (NZnOC) represents a new nutritional additive for the animal husbandry industry. However, the mechanism by which NZnOC mediates beef cattle growth and intestinal health is not fully understood. This study aimed to investigate the effects of carbon loaded with nano-ZnO (NZnOC) supplementation on growth performance, gut microbiota, bile acid (BAs) metabolism and intestinal immunity in fattening cattle. Twenty cattle (16 ± 0.95 months) were randomly assigned to two dietary groups: CON (control, without feed additive) and NZnOC (diet supplemented with 80 mg NZnOC/kg diet dry matter basic) for 60 d. The colon digesta microbiota composition and BAs concentration were determined by microbiota metagenomics and gas chromatography methods, respectively. RESULTS: The results showed that the NZnOC-supplemented cattle had greater final weight, average daily gain and gain-to-feed ratio than those in the CON group. Cattle fed the NZnOC diet had a higher relative abundance of the secondary BAs synthesizing phyla Firmicutes, Tenericutes and Actinobacteria than those fed the CON diet. Dietary supplementation with NZnOC increased the relative abundance of the secondary BAs synthesis microbiota genera Clostridium, Ruminococcus, Eubacterium, and Brevibacillus in colon digesta. Cattle fed the NZnOC diet had increased activities of 3α-hydroxysteroid dehydrogenase (EC: 1.1.1.52) and bile acid-CoA ligase BaiB (EC: 6.2.1.7) in the colon digesta compared with those fed the CON diet. The primary BAs taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate acid were significantly decreased by dietary NZnOC supplementation, while the secondary BAs deoxycholic acid, taurolithocholic acid, beta-muricholic acid, 12-ketolithocholic acid and ursodeoxycholic acid were significantly increased. Dietary supplementation with NZnOC increased the mRNA abundance of G protein-coupled bile acid receptor 1, protein kinase cAMP-activated catalytic subunit alpha, cyclic-AMP response element binding protein 1 and interleukin (IL)-10 in the colon mucosa of cattle, while the mRNA abundance of tumor necrosis factor and IL-1ß were significantly decreased. CONCLUSIONS: In summary, dietary supplementation with NZnOC can facilitate the growth performance and intestinal immune function of cattle by improving BAs metabolism. NZnOC can be supplemented in the diet as a safe regulator of gut microbiota and as a feed additive in the ruminants industry.


Subject(s)
Carbon , Metagenomics , Cattle , Animals , Diet/veterinary , Bile Acids and Salts , Immunity
13.
Front Pediatr ; 10: 1044309, 2022.
Article in English | MEDLINE | ID: mdl-36440346

ABSTRACT

Objective: To evaluate the advantages and disadvantages of da Vinci robot and laparoscopy in treating pediatric choledochal cysts. Methods: We retrospectively analyzed clinical data from forty-two children diagnosed with choledochal cysts in our hospital from January 2018 to January 2021. Twenty children underwent da Vinci robotic surgery, and the others underwent traditional laparoscopy. We compared differences in general information and preoperative, intraoperative, and postoperative differences between the two surgical groups. Results: There was no statistically significant difference in age, gender, weight, type, maximum cyst diameter, preoperative C-reactive protein (CRP) value, postoperative complication rate, and postoperative pain score between the two surgical groups (P > 0.05). The average age of the robot-assisted group was 3.62 ± 0.71 years old (range = 1-12 years). There were nineteen cases of Todani type I, one patients of other types, and the maximum cyst diameter was 35.45 ± 9.32 mm (range = 12-56 mm). In the laparoscopic group, the average age was 3.08 ± 0.82 years old (range = 3-10 years). Twenty-one patients had Todani type I, and one had other types. The maximum cyst diameter was 31.94 ± 8.64 mm (range = 10-82 mm). The robot-assisted group had better abdominal drainage, postoperative CRP value, fasting time, and discharge time than the laparoscopic group (P < 0.05). Conclusion: Compared with laparoscopy, the da Vinci system has the advantages of less tissue damage, faster recovery, and better healing in the treatment of children with congenital choledochal cysts. With technological advancements and an increased number of experienced surgeons, robotic surgery may become a new trend in surgery.

14.
Anal Chem ; 94(43): 14917-14924, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36269144

ABSTRACT

Thiols are essential metabolites associated with redox imbalances and metabolic disorders in diseases. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) facilitates imaging of metabolites in tissue, but imaging of thiols remains challenging. Here we developed a method to visualize thiols using a stable isotope-labeled (SIL) MALDI probe, a mixture of unlabeled and deuterium-labeled reagents that provided adduct signals at [M]+ and [M + 3]+, to identify endogenous thiols in tissue. A series of MALDI probe candidates were rationally designed, and the structure-effect relationships were determined. First, the reactivity of different warheads toward the thiol group was evaluated, and maleimide was the best for in situ derivatization. Second, an acridine fragment showed the best improvement in MS responses. Third, a permanent charge was introduced for detection improvement in the positive mode. Finally, the hydrogens of methyl group were replaced by deuterium atoms, obtaining the novel SIL MALDI probe and thus facilitating significantly the annotation of thiols. The finally obtained D0/D3-9-((2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)carbamoyl)-10-methylacridin-10-ium iodide (D0/D3-MaI-MADA) enabled direct MSI of thiols in the fine structures of human liver tumors without a reduction procedure. Our work built a SIL MALDI probe for the first time and provided a strategy for the rational design of MALDI probes.


Subject(s)
Acridines , Sulfhydryl Compounds , Humans , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Deuterium , Maleimides
15.
J Hum Genet ; 67(12): 687-690, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35996014

ABSTRACT

BACKGROUND: Recent researches on Parkinson's disease (PD) pathogenesis discovered the correlation between PD and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) dysfunction and reduction of PPARGC1A gene expression. Hence, we detected PPARGC1A rare variants to clarify their effect on PD risk in a large population of PD patients in mainland China. METHODS: We applied whole-exome sequencing (WES) to 1917 patients with early-onset or familial PD and 1652 controls (WES cohort), and whole-genome sequencing (WGS) to 1962 patients with sporadic late-onset PD and 1279 controls (WGS cohort). To identify PPARGC1A rare variants, we used burden analysis to assess the relationship between PPARGC1A rare variants and PD susceptibility. RESULTS: 30 rare missense variants in the cohort WES and 21 missense variants in the cohort WGS have been detected in the study and PPARGC1A missense variants are significantly associated with early-onset and familial PD susceptibility in our study (P = 0.012), which supports evidence that PPARGC1A rare variants are involved in the onset of early-onset and familial PD. CONCLUSIONS: The study suggested that PPARGC1A rare variants may contribute to the risk of early-onset and familial PD.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/genetics , Exome Sequencing , Cohort Studies , China/epidemiology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
16.
J Pediatr Urol ; 18(4): 516.e1-516.e9, 2022 08.
Article in English | MEDLINE | ID: mdl-35659823

ABSTRACT

BACKGROUND: Transvesicoscopic approaches for ureteral reimplantation (UR) are effective surgical techniques with which to resolve vesicoureteral reflux (VUR) or primary obstructive megaureter (POM) in pediatric patients. However, the effectiveness of different UR surgical methods for these two diseases is still unclear. PURPOSE: To compare the effects of Cohen's cross-trigonal and Politano-Leadbetter techniques in children in need of UR. METHODS: A retrospective chart review was performed for consecutive patients who underwent UR at our institution between May 2018 and November 2019, including those treated for vesicoureteral reflux (VUR) or primary obstructive megaureter (POM). Patients who underwent Cohen's technique included in Group C, and those who underwent the Politano-Leadbetter technique were included in Group P. Patient characteristics, perioperative parameters, and short-term postoperative outcomes were compared. RESULTS: Forty-six patients who underwent unilateral UR were included in the analysis. At presentation, those in Group P (N = 22, 12 diagnosed with VUR and 10 with POM) did not differ from those in Group C (N = 24, 12 diagnosed with VUR and 12 with POM) with respect to age, sex, disease type or severity. For VUR patients, reflux was clinically resolved for all patients in both groups; however, only a 75% resolution rate was observed in Group C, with 3 patients experiencing persistent low-grade, clinically insignificant reflux, while a 100% resolution rate was found in Group P (P > 0.05). Among POM patients, the obstruction was resolved for all those in Group P and for 90% of those in Group C; this difference was also not statistically significant (P > 0.05). At the 1-year follow-up, the ureteral diameter (P < 0.05) and anterior-posterior renal pelvic diameter (APRPD) (P < 0.05) of Group P were significantly reduced, and differential renal function (DRF) (P < 0.05) was slightly improved compared with that in Group C in both VUR and POM patients. CONCLUSIONS: Politano-Leadbetter and Cohen are both reliable techniques for UR in children with VUR or POM, and the short-term outcomes of these methods in solving reflux and obstruction are comparable. Besides traditional Cohen's technique, Politano-Leadbetter's technique maybe a potential choice for ureteral reimplantation in children.


Subject(s)
Ureter , Vesico-Ureteral Reflux , Child , Humans , Vesico-Ureteral Reflux/surgery , Retrospective Studies , Urologic Surgical Procedures/methods , Ureter/surgery , Replantation/methods , Treatment Outcome
17.
Fitoterapia ; 159: 105199, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35452745

ABSTRACT

Eight new sesquiterpenoid dimers, artatrovirenolides A-H (1-8), along with three known analogues (9-11), were isolated from Artemisia atrovirens by using the LC-MS guided isolation. Compound 1 was a compound dimerized from a guaianolide and a 1,10-seco-guaianolide unit while others were from two guaianolide units. Their structures were established by comprehensive analysis of spectroscopic data, and their absolute configurations were determined by the aid of time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. Compound 8 showed anti-inflammatory effect in LPS-stimulated BV-2 microglial cells at 1 µM, while compounds 1, 2, 5, and 6 inhibited microglial inflammation at 10 µM.


Subject(s)
Artemisia , Sesquiterpenes , Anti-Inflammatory Agents/pharmacology , Artemisia/chemistry , Microglia , Molecular Structure , Nitric Oxide , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology
18.
Front Pediatr ; 10: 720611, 2022.
Article in English | MEDLINE | ID: mdl-35281237

ABSTRACT

Background and Objective: Kaposiform hemangioendothelioma (KHE) is a rare, aggressive and borderline vascular tumor mainly occurring in infants and children. The aim of this study was to determine the health-related quality of life (HRQOL) in children with KHE. Measures: A total of 91 children with KHE participated in this cross-sectional study. The HRQOL was assessed by the age-specific Pediatric Quality of Life Inventory Version 4.0 (PedsQL™ 4.0) Infant Scales, Family Information Form (FIF), Family Impact Module (FIM) and Generic Core Scales (GCS). For comparison, demographically matched healthy children were recruited as a control group. The main outcome measure of HRQOL was analyzed in the two groups. We determined related factors that influenced the HRQOL in children with KHE and their parents by using a stepwise multiple regression analysis. Results: The study found that the scores of each item in the family impact module (FIM) were lower than 75, which suggesting that KHE can make the parents of patients in a state of poor quality of life. The scores of physiological and psychosocial domains in all age groups of patients with KHE were lower than those of normal children (P < 0.01). Activity dysfunction is the factor influencing the physiological function score of all-age patients. KMP is the factor influencing the psychosocial function score of all-age patients. Conclusions: The findings presented here suggest that patients with KHE have a poor HRQOL. KMP and activity dysfunction are risk factors for poor HRQOL in patients with KHE. However, lesion size, lesion location and education level of the mother and father were not related to the HRQOL.

19.
Thorac Cancer ; 13(7): 986-996, 2022 04.
Article in English | MEDLINE | ID: mdl-35166026

ABSTRACT

BACKGROUND: Circular RNAs (circRNAs) are key regulators in oncogenesis and chemoresistance of human cancers. Herein, we focused on the roles of circ_0002360 in regulating lung cancer progression and cisplatin (DDP) resistance. METHODS: The detection of circ_0002360, microRNA-6751-3p (miR-6751-3p) and zinc finger protein 300 (ZNF300) was conducted via reverse transcription-quantitative polymerase chain reaction assay. Cell sensitivity was determined using cell counting kit-8 assay. Proliferation detection was performed by colony formation assay and EdU assay. The migrated cells were examined via transwell assay. Cell apoptosis analysis was carried out through flow cytometry and caspase 3 activity assay. Western blot was used to examine the protein levels. Target interaction was confirmed through dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ_0002360 function in vivo was performed via xenograft tumor assay. RESULTS: Circ_0002360 was overexpressed in DDP-resistant lung cancer tissues and cells. Silencing circ_0002360 inhibited DDP resistance, proliferation and migration but enhanced apoptosis of DDP-resistant cells. Circ_0002360 could elevate ZNF300 expression. DDP resistance and lung cancer progression were also impeded by ZNF300 downregulation. ZNF300 overexpression reversed the function of circ_0002360 knockdown in DDP-resistant lung cancer cells. The regulation of circ_0002360 for ZNF300 was achieved by sponging miR-6751-3p. Circ_0002360 promoted DDP resistance in xenograft mice through mediating the miR-6751-3p/ZNF300 axis. CONCLUSION: Circ_0002360 targeted miR-6751-3p to regulate ZNF300 level, thus elevating DDP resistance and promoting the malignant progression of lung cancer cells.


Subject(s)
Lung Neoplasms , MicroRNAs , Animals , Cell Proliferation , Cisplatin/pharmacology , Cisplatin/therapeutic use , Drug Resistance, Neoplasm , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Mice , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Repressor Proteins , Xenograft Model Antitumor Assays
20.
Colloids Surf B Biointerfaces ; 211: 112296, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35030389

ABSTRACT

Incomplete removal of tumor cells and insufficient osseointegration are the main causes of bone tumor recurrence and implantation failure. In the present study, a multifunctional titanium-based bioactive implant for near-infrared-triggered synergy therapy to overcome these hurdles is engineered, composed of titanium dioxide (TiO2) nanoparticles doped with fluorine (F)/dopamine (PDA)/collagen. The TiO2 nanoparticles designed in this work can simultaneously exhibit excellent near-infrared-activated photothermal and photocatalytic properties. Besides, the layer designed in this work show excellent anti-tumor activity under irradiation with 808 nm light due to the synergetic effect of hyperthermia and reactive oxygen species (ROS), and Saos-2 cells can be eradicated within 10 min. Moreover, modification of PDA and collagen endue the Ti alloy excellent osteogenic activity.


Subject(s)
Hyperthermia, Induced , Osteosarcoma , Cell Differentiation , Humans , Osteogenesis , Osteosarcoma/therapy , Prostheses and Implants , Titanium/pharmacology
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